This proposal is a multidisciplinary approach to characterize the pathophysiologic, biochemical and morphologic factors involved in duodenal ulcer disease using animal model systems. We will concentrate on the elucidation of early neurohormonal and biochemical (functional) morphologic changes during chemically induced duodenal ulceration. Recently, we developed simple and easily reproducible models of this disease by administering chemicals, e.g., propionitrile and cysteamine in the rat. The model is very similar both in functional and morphologic features to human duodenal ulcer disease. In our studies we will employ rats and rabbits, and use animal experiments, organ culture, biochemical, histochemical, radioautographic, light and electron microscopic techniques. We would like (1) to investigate the role of neurohormonal (e.g., dopamine, noradrenaline, serotonin, gastrin, somatostatin) changes in the brain and peripheral organs in the pathogenesis of duodenal ulceration, (2) to study the biochemical-functional morphologic alterations in gastric and duodenal mucosa by organ culture techniques (epithelial cell proliferation, protein and mucus glycoprotein synthesis) and in animal experiments (histochemistry) under the influence of duodenal ulcerogens, and (3) to measure gastric and pancreatic (i.e., duodenal) secretion during chemically induced duodenal ulceration. These results may yield insight into the etiology and pathogenesis of duodenal ulcer in general. Furthermore, the studies may have public health implications on the ulcerogenic action of some chemicals with which man might have prolonged and/or repeated contacts.